Background
Evaluating the molecular characteristics of brain metastases is limited by difficult access and by the blood–brain barrier, which prevents circulating tumor DNA (ctDNA) from entering the blood. In this study, we aimed to compare the sequencing results from cerebrospinal fluid (CSF) ctDNA versus plasma ctDNA, plasma circulating tumor cells (CTCs), and brain tissue specimens from patients with brain metastasis from non‐small cell lung cancer (NSCLC).
Methods
This was a prospective study of 21 consecutive patients with NSCLC and brain metastasis diagnosed between April 2018 and January 2019. Samples of CSF and peripheral blood were obtained from all 21 patients. Brain tissues were obtained from five patients after surgical resection. Next‐generation sequencing was performed using the Ion system. Single nucleotide variants (SNVs) and small insertions or deletions (indels) were searched.
Results
Mutations were detected in the CSF ctDNA of 20 (95.2%) patients. The detection rate of epidermal growth factor receptor (EGFR) mutations in CSF ctDNA was 57.1% (12/21) whereas this rate was only 23.8% (5/21) in peripheral blood ctDNA and in CTCs. EGFR mutations were found in the CSF of 9 of 11 (81.8%) patients with leptomeningeal metastases, as compared with three of 10 (30%) patients with brain parenchymal metastases. Mutations were also detected in KIT, PIK3CA, TP53, SMAD4, ATM, SMARCB1, PTEN, FLT3, GNAS, STK11, MET, CTNNB1, APC, FBXW7, ERBB4, and KDR (all >10%). The status of EGFR and TP53 mutations was consistent between CSF ctDNA and brain lesion tissue in all five patients.
Conclusion
Sequencing of CSF ctDNA revealed specific mutation patterns in driver genes among patients with NSCLC and brain metastasis.
Key points
In some small‐sample studies, the importance of cerebrospinal fluid in guiding the treatment of cancerous brain lesions has been verified in that it may reflect genomic mutations of brain tumors relatively accurately.
Cerebrospinal fluid is a new form of liquid biopsy that can be helpful in improving the management of patients with brain metastasis from non‐small cell lung cancer by detecting genetic abnormalities specific to brain metastases.
Seedlings of Iris lactea var. chinensis (Fisch.) Koidz. and I. tectorum Maxim. were subjected to 0-160 mg l(-1) Cd in hydroponic system and harvested after 42 days to determine effects on root and shoot dry mass. A subset of 16-day-old seedlings was exposed to 1000 mg l(-1) Cd to characterize sub-cellular localization of Cd in root cells. The Cd contents in the shoots of I. lactea var. chinensis reached 529 microg g(-1 )dry weight (dw) at 80 mg l(-1) Cd treatment and in the shoots of I. tectorum reached 232 microg g(-1) dw at 40 mg l(-1) Cd treatment, without showing signs of visible toxicity. The Cd contents in the shoots of both two test species exceeded 100 microg g(-1), the critical value of Cd hyperaccumulator. The indices of tolerance (ITs) of I. lactea var. chinensis were higher than those of I. tectorum under 10-160 mg l(-1)Cd stress. Sub-cellular localization of Cd in root cells was evaluated using transmission electron microscopy (TEM) and Cd deposits were found in the cell walls, in the cytoplasm and on the inner surface of xylem vessels in the root tip of I. lactea var. chinensis and I. tectorum. A few cells in the root tip of I. tectorum were necrotic. The results showed that the tolerance and accumulation of Cd by I. lactea var. chinensis were higher than those of I. tectorum, suggesting that I. lactea var. chinensis has potential application in phytoremediation.
BackgroundOvarian cancer (OC) is associated with high mortality in gynecological oncology; this is mainly due to the low diagnosis rate. Exosomal miRNA has demonstrated potential as a tumor biomarker. We aimed to explore the diagnostic potential of serum exosomal miR-1307 and miR-375 for OC.MethodsThe first six candidate miRNAs were selected from the previous literature. The relative quantification of qRT-PCR was used to screen for the stability of exosomal miRNAs, followed by validation of the cohort. ROC analysis was employed to analyze the specificity and sensitivity of exosomal miRNA.ResultsMiR-1307 and miR-375 were confirmed stably existing in serum exosomes of OC. Moreover, miR-1307 and miR-375 were both significantly up-regulated in serum exosomes of OC compared to ovarian benign and healthy groups. The overexpressed miRNAs showed independent diagnostic power and enhanced the diagnostic accuracy of traditional biomarkers when combined with CA-125 and HE4. MiR-1307 was associated with tumor staging, and miR-375 was associated with lymph node metastasis of OC.ConclusionOur results suggest that serum exosomal miR-1307 and miR-375 could serve as potential tumor biomarkers to improve diagnostic efficiency for OC.
Our findings indicated that high levels of preoperative NLR might be a potential biomarker of worse response to first-line platinum-based chemotherapy and poor clinical outcomes in patients with SOC. Further validation of this easily available parameter as a potential stratification tool in prospective studies should be encouraged.
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